Co-administration of irbesartan reduced aliskiren Cmax up to 50% after multiple dosing.

P-glycoprotein Effects

Pgp (MDR1/Mdr1a/1b) was found to be the major efflux system involved in absorption and disposition of aliskiren in preclinical studies. The potential for drug interactions at the Pgp site will likely depend on the degree of inhibition of this transporter.

Co-administration of aliskiren with Pgp substrates or weak to moderate inhibitors such as atenolol, digoxin, and amlodipine did not result in clinically relevant interactions.

Co-administration of atorvastatin, a potent Pgp inhibitor, resulted in about a 50% increase in aliskiren Cmax and AUC after multiple dosing.

Ketoconazole

Co-administration of 200 mg twice-daily ketoconazole, a potent Pgp inhibitor, with aliskiren resulted in an approximate 80% increase in plasma levels of aliskiren. A 400 mg once-daily dose was not studied but would be expected to increase aliskiren blood levels further.

Cyclosporine

Co-administration of 200 mg and 600 mg cyclosporine, a highly potent Pgp inhibitor, with 75 mg aliskiren resulted in an approximately 2.5 fold increase in Cmax and 5 fold increase in AUC of aliskiren. Concomitant use of aliskiren with cyclosporine is not recommended.

The effects of aliskiren on warfarin pharmacokinetics have not been evaluated in a well-controlled clinical trial.

Furosemide

When aliskiren was co-administered with furosemide, the AUC and Cmax of furosemide were reduced by about 30% and 50%, respectively.

OVERDOSAGE

Limited data are available related to overdosage in humans. The most likely manifestation of overdosage would be hypotension. If symptomatic hypotension should occur, supportive treatment should be initiated.